The main objective of this study was to analyze changes in the antiproliferative effect of vitamin D3, in the form of calcitriol and calcidiol, via its combined application with all-trans retinoic acid (ATRA) in osteosarcoma cell lines. The response to treatment with calcitriol and calcidiol alone was specific for each cell line. Nevertheless, we observed an enhanced effect of combined treatment with ATRA and calcitriol in the majority of the cell lines. Although the levels of respective nuclear receptors did not correlate with the sensitivity of cells to these drugs, vitamin D receptor (VDR) upregulation induced by ATRA was found in cell lines that were the most sensitive to the combined treatment. In addition, all these cell lines showed high endogenous levels of retinoic acid receptor α (RARα). Our study confirmed that the combination of calcitriol and ATRA can achieve enhanced antiproliferative effects in human osteosarcoma cell lines in vitro. Moreover, we provide the first evidence that ATRA is able to upregulate VDR expression in human osteosarcoma cells. According to our results, the endogenous levels of RARα and VDR could be used as a predictor of possible synergy between ATRA and calcitriol in osteosarcoma cells.

• Klíčová slova
• all-trans retinoic acid, calcidiol, calcitriol, osteosarcoma, retinoic acid receptor α, vitamin D receptor,
• MeSH
• alfa receptor kyseliny retinové metabolismus   MeSH
• kalcifediol aplikace a dávkování   MeSH
• kalcitriol aplikace a dávkování   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• osteosarkom farmakoterapie   metabolismus   MeSH
• protinádorové látky aplikace a dávkování   MeSH
• protokoly protinádorové kombinované chemoterapie MeSH
• receptory kalcitriolu metabolismus   MeSH
• screeningové testy protinádorových léčiv MeSH
• tretinoin aplikace a dávkování   MeSH
• vitaminy aplikace a dávkování   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• alfa receptor kyseliny retinové MeSH
• kalcifediol MeSH
• kalcitriol MeSH
• protinádorové látky MeSH
• receptory kalcitriolu MeSH
• tretinoin MeSH
• vitaminy MeSH

For decades, retinoids and their synthetic derivatives have been well established anticancer treatments due to their ability to regulate cell growth and induce cell differentiation and apoptosis. Many studies have reported the promising role of retinoids in attaining better outcomes for adult or pediatric patients suffering from several types of cancer, especially acute myeloid leukemia and neuroblastoma. However, even this promising differentiation therapy has some limitations: retinoid toxicity and intrinsic or acquired resistance have been observed in many patients. Therefore, the identification of molecular markers that predict the therapeutic response to retinoid treatment is undoubtedly important for retinoid use in clinical practice. The purpose of this review is to summarize the current knowledge on candidate markers, including both genetic alterations and protein markers, for retinoid resistance and sensitivity in human malignancies.

• Klíčová slova
• Acute myeloid leukemia, Breast carcinoma, Cell differentiation, Neuroblastoma, Pancreatic ductal adenocarcinoma, Predictive biomarkers, Retinoid resistance, Retinoid sensitivity, Retinoids,
• MeSH
• biologické markery MeSH
• buněčná diferenciace účinky léků   MeSH
• chemorezistence MeSH
• fytogenní protinádorové látky chemie   farmakologie   terapeutické užití   MeSH
• klinické zkoušky jako téma MeSH
• lidé MeSH
• management nemoci MeSH
• nádory diagnóza   farmakoterapie   genetika   metabolismus   MeSH
• prognóza MeSH
• receptory kyseliny retinové chemie   metabolismus   MeSH
• retinoidy chemie   farmakologie   terapeutické užití   MeSH
• výsledek terapie MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• biologické markery MeSH
• fytogenní protinádorové látky MeSH
• receptory kyseliny retinové MeSH
• retinoidy MeSH